LITERATURE REVIEW

PAIN MANAGEMENT IN ACUTE PANCREATITIS

Presented by :
Made Sebastian Dwi Putra Hardika
(1202006093)

Supervisor :
Dr. dr. I Wayan Suranadi, Sp.An, KIC

CO-ASSISTANCE IN CLINICAL CLERKSHIP

ANESTHESIOLOGY DEPARTMENT
FACULTY OF MEDICINE UDAYANA UNIVERSITY / SANGLAH HOSPITAL
MAY 2016

PREFACE

Praise and gratitude the author prayed to the presence of God so that the author can
finish a literature review entitled Pain Management in Acute Pancreatitis right on
time. This literature review is done in order to participate in the co-assistance in clinical
clerkship of Anesthesiology Department Faculty of Medicine Udayana University /
Sanglah Hospital.
In completing this literature review, author receives great assistance and guidance in
either information or morale. For that, in this occasion author wants to give greatest
gratitude for :
1.

Dr. dr. I Wayan Suranadi, Sp.An, KIC as my mentor for his advice and guidance

2.

All the staff of Anesthesiology Department in Sanglah Hospital

3.

All parties who has given me so much help in organizing this literature review

Author realize that this literature review is far from perfect, therefore constructive
critiques and advices are expected in order to develop its perfection. Lastly, author
hopes this literature review will be a beneficial source in science and medicine.

Denpasar, May 2016

Author

ii

TABLE OF CONTENT

Page
TITLE ........................................................................................................................

PREFACE.................................................................................................................. ii
TABLE OF CONTENT ............................................................................................ iii
CHAPTER I

INTRODUCTION ........................................................................... 1

CHAPTER II

LITERATURE REVIEW ................................................................ 2

2.1

Definition and Epidemiology of Acute Pancreatitis ............................... 2

2.2

Etiology of Acute Pancreatitis ................................................................ 3

2.3

General Principle of Pain in Acute Pancreatitis ..................................... 3

2.4

Pathophysiology and Innervation of Pain in Acute Pancreatitis ............ 5

2.5

Pain Management in Acute Pancreatitis ................................................. 9

CHAPTER III CONCLUSION ............................................................................... 13

REFERENCE

iii

CHAPTER I
INTRODUCTION

Acute pancreatitis is an acute inflammatory process of the pancreas that

may also involve adjacent tissues and/or remote organ systems. It happens when
digestive juices become active inside the pancreas, causing swelling, bleeding and
damage to the pancreas and its blood vessels.1 Recent studies show the incidence
of acute pancreatitis varies between 4.9 and 73.4 cases per 100,000 worldwide.2 It
is a serious condition and can lead to further problems.
Pain is the main symptom in acute pancreatitis. Abdominal pain occurs
during almost all episodes of acute pancreatitis. Typically, there is epigastric or
upper abdominal pain, which rapidly becomes more severe and accompanied by
nausea and vomiting, leading the patient to ask for attention at the emergency
department. It is thought that the pain is caused by the action of activated
pancreatic enzymes and the release of cytokines by inflammatory cells. Pain is
transmitted along the different sensory fibers found throughout the pancreas to the
celiac plexus and via the splanchnic nerves to the sympathetic chain between T5
and T9.3 This pain problem is raising the need of sufficient pain control.
Pain control is an important part of the supportive management of patients
with acute pancreatitis. Treatment of pain during acute pancreatitis continues to be
a challenging task in the clinical routine. A consensus has not yet been reached as
to which analgesics are useful in reducing pain from acute pancreatitis.4 The
management of this pain follows the same general rules as the treatment of other
acute pain, namely the staged use of analgesics, but the oral route is ruled out.5
This paper is focusing on what is the most appropriate strategy approach in
managing acute pancreatitis pain, how to choose any class and type of analgesics,
and the principle of how each group of analgesics modify or manage the pain. By
understanding the effect of each analgesics which most widely used as the
treatment of acute pancreatitis pain, physicians could treat the pain accurately
based on the degree of the pain and the severity of the disease which may also
allow conclusions on the cause of acute pancreatitis and as the result it could be
easier to do further examination to the patient.

CHAPTER II
LITERATURE REVIEW

2.1

Definition and Epidemiology of Acute Pancreatitis

Acute pancreatitis is the result of an inflammatory process involving the

pancreas that may also involve adjacent tissues and/or remote organ systems
caused by the release of activated pancreatic enzymes with sudden onset and
duration of less than 6 months.6 The activated pancreatic enzymes digest
pancreas, causing edema, vascular damage, hemorrhage and necrosis of pancreatic
tissue.7 Acute pancreatitis may present as mild or severe. Milder forms of acute
pancreatitis accounts for 80% of all cases and is associated with minimal organ
dysfunction and fewer complications. However, severe forms involve necrosis of
pancreatic tissue, which occurs in 20% of cases, and results in increased
complications and mortality.6,8,9
The incidence of pancreatitis varies in different countries and depends on
cause, like alcohol, gallstones, metabolic factors and drugs. Acute pancreatitis is a
common acute surgical condition associated with high morbidity and mortality in
severe cases with annual incidence worldwide is 4.9-73.4 cases per 100,000
people.10 In German, the incidence rate of acute pancreatitis is 17.5 cases per
100,000 people. In Finland, 73.4 cases per 100,000 people, the same incidence
rate is reported in Australia. No data were reported on the incidence of this disease
in Indonesia, but in the research conducted by Nurman on 1990 showed that about
1 from 3 patient with severe upper abdominal pain is acute pancreatitis patient.6
Acute pancreatitis is a potential fatal disease with high overall mortality (2.1%7.8%). For the severe acute pancreatitis, mortality may be as high as 25%.11
Acute pancreatitis occurs more frequently in men. Differences in the
occurrence of pancreatitis between males and females are likely due to different
frequencies of various pancreatitis risk factors associated with each gender. Men
are more likely to have alcohol-induced pancreatitis, whereas in women have a
predilection for the development of gallstones, and therefore, are more likely to
develop gallstone-associated pancreatitis. By race, the risk of 35-64 years old

African-American descent is 10 times fold higher than in other group. The risk for
African-Americans is always higher than Caucasians in all ages group.2,6,8

2.2

Etiology of Acute Pancreatitis

The most common causes of acute pancreatitis in the Western population

are alcohol and gallstones, but many other causes have also been described and
regardless of the trigger, there is an underlying common pathogenic outcome.
Gallstones continue to be the leading cause of acute pancreatitis in most series
(30-60%). Alcohol is the second most common cause, responsible for 15-30%
cases, but the mechanism of injury is not well understood.10 If there is no other
causes, serum triglyceride levels >11.3 mmol/L or >1000 mg/dl must be
considered as the cause of acute pancreatitis because hypertriglyceridemia is
found in 1.3-3.8% of cases. Acute pancreatitis occurs in 5-20% of patients
following

endoscopic

retrograde

cholangiopancreatography

(ERCP).

Approximately 2-5% of cases of acute pancreatitis are drug-related. Some drugs

that could cause acute pancreatitis are azathioprine, 6-mercaptopurine,
sulfonamides, valproic acid, tetracycline and anti-HIV drugs. Drugs cause
pancreatitis either by a hypersensitivity reaction or by the generation of a toxic
metabolite, although in some cases it is not clear which of these mechanisms is
operative.6,9

2.3

General Principle of Pain in Acute Pancreatitis

Abdominal pain is the most frequently reported symptom in acute

pancreatitis and occurs in almost every case. Visceral type of pain is found in
acute pancreatitis patient. This type of pain is transmitted by C nerve fibers that
commonly found in muscle, periosteum, mesentery, peritoneum and viscera. Most
of nociception from abdominal visceral is conveyed by this type of fiber and tends
to be interpreted as dull, cramping, burning sensation and poorly localized. It is
also more likely to have greater variation and duration compared to the somatic
pain. It occurs since the visceral organs in the abdomen transmit sensory afferent
stimuli to both side of the spinal cord. Moreover, visceral pain is poorly localized
due to lower number of nerve endings in visceral organ than other organs such as

the skin and since the innervations of viscera is multisegmental. Because the
pancreas does not contact the somatically innervated parietal peritoneum, sharply
localized pain usually does not occur.12,13
The patient experiences pain either in the epigastrium alone or in the
epigastrium and left upper quadrant of abdomen, or throughout the entire upper
abdomen and associated with less abdominal rigidity. Pain radiates through to the
back in about half of the patients, presumably because of retroperitoneal irritation.
Occasionally, the pain is diffuse or radiates to the lower abdomen. Pain reported
in the right or left lower abdomen is probably caused by pancreatic exudates
spreading via the transverse mesocolon to the cecum or along the left colon. Pain
is usually more intensive in the upper than in the lower abdomen. Rarely, the pain
radiates to the chest.14,15,16
Pancreatic abdominal pain is commonly characterized by violent onset. In
some patients, it increases gradually and reaches maximum intensity after several
hours, but in most cases it starts suddenly and reaches its maximum intensity
within 10-30 minutes. Usually, the initial pain in acute pancreatitis lasts only a
few days and disappears spontaneously when the local inflammatory reaction
improves. The pain is often very severe, boring in character and constant in
duration. The intensity of pain rarely fluctuates and when not treated, can persist
for several hours or even days. It is the intensity and persistence of the pain that
usually causes patients to seek medical attention. On a scale of 1-10 (10 equals
intolerable, agonizing pain), the severity of pain in acute pancreatitis is often
described as 10. Duration of abdominal pain during first attacks of acute
pancreatitis showed that pain associated with alcoholic pancreatitis usually lasts
longer than pain associated with biliary pancreatitis.14,15,17 But there is no study
that has shown any correlation between the degree of pain and the severity of the
pancreatitis. However, it tends to last longer in patients with severe pancreatitis
and contributes to their hemodynamic instability.3
Similarly, the presence or absence of pain is an important factor in
resuming normal eating. A relationship has been shown between prolonged pain
and its recurrence when oral feeding is started.3 Eating food can worsen the pain.
It may require the insertion of a nasogastric tube for relief.17 Most patients have

difficulty finding a position that provides pain relief. The pain is typically
exacerbated in the supine position and patients with acute pancreatitis often prefer
to sit with the dorsal spine flexed and the knees drawn up to the abdomen or
sitting up and flexing forward, which frees the retroperitoneal space.15,16,17,18
The other clinical signs that may be noted and accompanied the specific
pain in acute pancreatitis, varying with the severity of the disease as
follow:3,12,14,19
Nausea and vomiting are often present along with accompanying anorexia.
Both may be caused by abdominal pain, by anterior extension of the
retroperitoneal inflammation to the region of the posterior wall of the
stomach, or by the development of a significant fluid collection in the
lesser sac compressing the body of the stomach and causing obstruction.
Fever and tachycardia are common abnormal vital signs and hypotension
may be present due to dehydration and severe pain.
Abdominal tenderness, muscular guarding and distension are observed in
most patients, particularly in the epigastrium. Bowel sounds are often
diminished or absent due to gastric and transverse colonic ileus.
Tachypnea may be evident due to pain, fever or pulmonary involvement.
Some patients breath shallowly (dyspnea), which may be caused by
irritation of the diaphragm that resulting from pancreatic inflammatory
exudates and abdominal pain.
In severe cases, hemodynamic instability is evident and hematemesis or
melena sometimes develops. In addition, patient with severe acute
pancreatitis are often pale, diaphoretic and listless.
Sometimes, the pain may recur during the course of illness when the
complications such as intra-abdominal infection, pancreatic pseudocyst, intraabdominal hemorrhage, colon perforation, obstruction or fistulization and
multiorgan system failure develop.3,19

2.4

Patophysiology and Innervation of Pain in Acute Pancreatitis

Acute pancreatitis is a complex multi-step process. The factors that

initially activate the pain pathway in acute pancreatitis are still unclear.

Pathological activation of sensory neurons and inflammatory sequelae constitute

what is known as neurogenic inflammation which appears to be important in
many organ systems, including pancreas.20 The pathologic mechanism responsible
for the development of acute pancreatitis is believed to be autodigestion by
inappropriate intrapancreatic activation of proteolytic enzymes (primarily trypsin)
and release of other substances, such as elastase, phospholipase A, lipase, and
vasoactive polypeptide. The destruction of pancreatic parenchyma during acute
pancreatitis quickly induces an inflammatory reaction at the site of injury. The
initial cellular response involves the infiltration of polymorphonuclear leukocytes
into the perivascular regions of the pancreas. Within a few hours, macrophages
and lymphocytes accumulate and phagocyte-derived oxygen radicals participate in
a primary injury to the pancreatic capillary endothelial cells. The increased
microvascular permeability facilitates margination and extravascular migration of
additional neutrophils and monocytes, amplifying the inflammatory process and
thereby causing hemorrhage, edema and pain. These can also lead to metabolic
consequences such as fever, hypotension, acidosis and acute respiratory distress
syndrome.16,20

Figure 1. Mechanisms underlying pancreatitis pain21

Damage to the endings of pancreatic afferent nerves could contribute to
their sensitization and activation. These afferent nerves are indicated to activate
during the onset and progression of acute pancreatitis. Neurogenic inflammation
is the inflammatory response elicited by the release of neuropeptides such as

substance P (SP) and calcitonin gene-related peptide (CGRP) from afferent nerve
endings. The release of SP and CGRP contribute to edema and vasodilatation in
the organ. Mediators such as bradykinin, leukotriene B4, pH <6.4, resulting from
pancreatic acinar cell damage are proposed to activate the endings of afferent
neurons to release SP and CGRP in the spinal cord and in the periphery. Therefore
modulating the activity of pancreatic sympathetic afferent nerves may not only
influence nociceptive signaling but the inflammatory process itself.20,21 The
sensation of pain in acute pancreatitis is transmitted along the different sensory
fibers found throughout the pancreas to the celiac plexus and then, via the
splanchnic nerves, to the sympathetic chain between T5 and T9. The nerve bodies
of these fibers are found in the dorsal root ganglia.3

Figure 2. Pathway of visceral sensory innervation12

The pancreas is richly innervated by a variety of myelinated or

unmyelinated nerve fibers, thick nerve bundles and aggregates of neural cell
bodies known as intrapancreatic ganglia. These ganglionic structures representing
the intrinsic component of the pancreatic innervations are randomly distributed
throughout the pancreatic parenchyma. The afferent system, which involved in
transmitting sensory to the central nervous system (CNS), is composed of thin
unmyelinated fibers. These fibers run with either the parasympathetic pathways
(vagus) or the sympathetic inputs (splanchnic nerves), of which cell bodies
processes can be located either in the dorsal root ganglia (the spinal afferents) or
in the nodose ganglia (vagal afferents). The extrinsic fibers belong to the
sympathetic and parasympathetic systems.22,23
Initially, the acutely inflamed pancreas is perceived as a deep dull pain. As
the inflammatory process involves the pancreatic visceral peritoneum, which
contains unnmyelinated nociceptive nerve endings, the pain becomes severe. At
this point, peritoneal signs develop. Further spread of the inflammatory process
involves the parietal peritoneum of the anterior abdominal wall. This results in the
rigid abdominal wall splinting seen in pancreatitis. The viscerosomatic reflex
from pancreas makes the generalized upper abdominal pain associated with acute
pancreatitis even more logical. The pancreas reflex is bilateral from T5 to T9. The
T5 through T9 dermatomes supply the upper abdominal wall. Spinal facilitation
produces segmental hyperalgesia. The bilateral movement of the pancreas reflex
results in sensitization of the entire upper abdominal wall. Pancreatic referred pain
in the mid to low thoracic region is a direct manifestation of the location of the
pancreas in association with the bilateral T5 through T9 paravertebral tenderness
of the viscerosomatic reflex.24
The parasympathetic (vagal) viscerosomatic reflex is found in the upper
cervical region (occiput to C2). It is unilateral with a greater incidence on the
right. This reflex is particularly useful for monitoring the progression of the
illness because its suboccipital location makes it easily accessible in the bedridden
patient. If pancreatitis develops as the result of gall stones, a gallbladder reflex
will be present at T10 right. If it develops in association with alcoholic hepatits,
slightly broader reaction from T9 to T10 right can be expected. The upper

gastrointestinal irritation associated with the nausea and vomiting that accompany
acute pancreatitis produces an upper gastrointestinal reflex pattern of occiput to
C2 left (vagus), T3 to T6 right (esophagus), T5 to T10 left (stomach) and T6 to T8
right (duodenum). The somatic findings paravertebrally in the upper cervical
region and from T5 to T9 bilaterally in association with the signs and symptoms
of acute pancreatitis are very useful information. As can readily be seen, the more
complex the presentation and the more intense the pathology, the greater area of
viscerosomatic reflex and paravertebral tissue texture change.24

2.5

Pain Management in Acute Pancreatitis

Pain in acute pancreatitis generally causes severe and persistent pain and

thus necessitates effective treatment. Effective treatment of pain is warranted in

the management and this does not hamper diagnosis or treatment.1,4 In addition to
increasing patient comfort, alleviating pain moderates the physiological response
to pain and immunological mechanism.25,26 An adequate pain treatment after
patients admission to the hospital is often a challenging task which requires
interdisciplinary management. One reason for the challenge behind pain
management is the high complexity of acute pancreatitis itself. Whereas mild to
moderate epigastric pain is often the single symptom of mild (edematous)
pancreatitis, patients with severe (necrotizing) acute pancreatitis often suffer from
severe pain attacks, pleural effusion, ascites and even multiple organ failure.5
There are several measures available to relieve pain. It is advisable for the
patient to fast, at least initially. This limits pancreatic stimulation and improves
the abdominal distension secondary to acute pancreatitis. When ileus is present,
passing a nasogastric tube may improve symptoms. Obviously, these measures
alone are not sufficient to control the pain as this requires suitable medication.
The management of abdominal pain associated with acute pancreatitis follows the
same general rules as the treatment of other acute pain, namely the staged use of
analgesics, but the oral route is ruled out. The pharmacologic treatment of
pancreatitis therefore requires parenteral or other alternative routes of
administration. Basically, since the pain is continuous, analgesics should be
prescribed at regular intervals or even as a continuous perfusion following an

initial loading dose to control the pain rapidly. Once the pain is under control,
analgesics may be prescribed as needed by the patient.3
An agreement has not yet been reached as to which analgesics are useful in
treating pain in patients with acute pancreatitis. It is hypothesized this results in a
clinician specific approach to the administration of analgesics. There is a wide
variety of analgesics are prescribed for patients with acute pancreatitis.1,4,5,18,27 In
clinical practice, the treatment of pain ranges and escalates from low-dose nonopioid analgesics to high-dose opioid analgesics. According to the World Health
Organization (WHO) regime, the pain treatment begins with low potent nonsteroidal anti-inflammatory drugs (NSAIDs) which may be sufficient in mild or
moderate pain due to acute pancreatitis and rises step by step up to highly potent
NSAIDs combine with opioids.5 Optimal pain relief seems to result from a
multimodal approach, combining a variety of medications and possibly
nonpharmacologic measures. With multimodal analgesia, also known as balanced
analgesia, the patient is given two or more analgesic agents and/or analgesic
measures. Each agent acts by a different mechanism and at a different site in the
nervous system. This method provides maximal pain relief by using lower drug
doses while minimizing adverse effects of any single agent.25,26

Figure 3. Stepped approach to pain management.5

The analgesic agents prescribed for a patient will depend on the cause and
type of the patients pain and on the individuals response to the treatment. A
patient may experience better pain relief or more adverse effects with a certain
opioid or NSAID versus another opioid or NSAID. If a patient is not experiencing
10

expected relief or is experiencing adverse effects, a trial of another agent in the

same analgesic class is warranted. The selection of the appropriate analgesic
therapy is based on the severity of the patients pain and his/her current analgesic
therapy. Pain intensity can be measured reliably in most patients with the use of
written or verbal numerical rating scales.25,26
In general, pain that is rated 4-5 or higher on a scale of 0-10 interferes with
a patients quality of life and is considered to be significant pain. Pain ratings of 1
to 4 correspond to mild pain, pain ratings of 5 to 6 represent moderate pain and
pain ratings of 7 to 10 mark severe pain.25,26 Patients with mild-to-moderate acute
pancreatitis pain were more likely to receive combination of NSAIDs (such as
metamizole and dexketoprofen) and weak opioids (such as tramadol). Patients
who have moderate-to-severe acute pancreatitis pain require the use of strong
opioids (such as morphine, pethidine and buprenorphine).4,8,11,18,20,28 Opiate
analgesics are administered to most patients with acute pancreatitis. According to
the study conducted by Perera et al., opioid constitute the main analgesic
administered during 87.8% episodes of care. Patients with alcohol-related acute
pancreatitis are more likely to receive opiate analgesics than those with gallstone
disease, and also with higher dose. Non-opiate analgesics are often
underutilized.18
Pain due to acute pancreatitis should be treated from the very onset of the
disease by regular analgesic administration. In general terms, patient-controlled
analgesia pumps are recommended. Staged treatment should be given.
Metamizole (2,000 mg every 6-8 hours intravenously) or tramadol (100 mg every
8 hours intravenously), with pethidine (50-100 mg subcutaneously as a single
dose) for rescue between doses. When pain control is satisfactory or the pain
disappears, the same dosage may be used on demand by the patient. However, if
the pain is not controlled, opioids become necessary. Until studies confirm the
safety of morphine and its derivatives, the use of pethidine (50-100 mg every 4
hours subcutaneously) or buprenorphine (0.3-0.6 mg every 6 hours parenterally;
0.2-0.4 mg every 6 hours sublingually; 0.002 mg/kg per hour as intravenous
continuous perfusion) is recommended.3

11

mild-tomoderate pain

moderate-tosevere pain

Figure 4. Pain management steps of acute pancreatitis3

Patients who require high doses of opioids for adequate pain control and
especially those with organ failure (mainly renal and/or respiratory failure),
should be treated with epidural anesthesia using either local anesthetics alone or
better with the combination of local anesthetics and opioids. This kind of
analgesics may be administered in addition to systemic opioids, the dose of which
can then be reduced, or can be used as the sole treatment.3,27

12

CHAPTER III
CONCLUSION

1.

Acute pancreatitis is an acute inflammatory process of the pancreas that

may also involve adjacent tissues and/or remote organ systems.

2.

Abdominal pain is a common feature of acute pancreatitis which

characterized by steady, boring epigastric pain that radiates to the flanks
and chest.

3.

Digestion of fatty tissue in the retroperitoneum could trigger local

inflammatory factors and lead to the generation of nociceptive stimuli
which is thought to be the mechanism of pain in acute pancreatitis.

4.

Alleviation of pain is an essential step in the management of acute

pancreatitis that begins by identifying the underlying cause and a diseasespecific treatment.

5.

Mild-to-moderate pain were more likely to receive combination of

NSAIDs (such as metamizole and dexketoprofen) and weak opioids (such
as tramadol) whereas moderate-to-severe pain require the use of strong
opioids (such as morphine, pethidine and buprenorphine).

13

REFERENCES
1.

Glen B, Dur A, Serinken M, Karcolu , Snmez E. Pain treatment in

patients with acute pancreatitis: a randomized controlled trial. Turk J
Gastroenterol. 2016. 27:192-6.

2.

Tenner S, Baillie J, DeWitt J, Vege SS. Management of acute pancreatitis.

Am J Gastroenterol. 2013. 108:1400-15.

3.

Martinez J, Perez-Mateo M. Guidelines for the treatment of pain in acute

pancreatitis. In: Dominguez-Munoz JE. Clinical Pancreatology for Practising
Gastroenterologists and Surgeons. 1st Edition. Massachusetts: Blackwell
Publishing Ltd. 2005. p. 87-94.

4.

Yokoe M, Takada T, Mayumi T, Yoshida M, Isaji S, Wada K, Itoi T, et al.

Japanese guidelines for the management of acute pancreatitis: Japanese
guidelines 2015. J Hepatobiliary Pancreat Sci. 2015. 22:405-32.

5.

Schorn S, Ceyhan GO, Tieftrunk E, Friess H, Demir IE. Pain management in

acute pancreatitis. Pancreapedia. 2015. 5:1-13.

6.

Pratama H. Tatalaksana pankreatitis akut. CDK-238. 2016. 43(3):190-4.

7.

Basurto OX, Rigau CD, Urrutia G. Opioids for acute pancreatitis pain
(review). Cochrane Database Syst Rev. 2013. 7:1-46.

8.

Banks PA, Conwell DL, Toskes PP. The management of acute and chronic
pancreatitis. Gastroenterology & Hepatology. 2010. 6(2):1-13.

9.

Greenberger NJ, Toskes PP. Acute and chronic pancreatitis. In: Fauci AS,
Braunwald E, Kasper DL, Hauser SL, Longo DL, Jameson JL, Loscalzo J.
Harrisons Principles of Internal Medicine. 17th Edition. New York: McGrawHill. 2008. p. 2005-17.

10. Nesvaderani M, Eslick GD, Cox MR. Acute pancreatitis: update on

management. MJA 2015. 202(8):420-4.
11. Meng W, Yuan J, Zhang C, Bai Z, Zhou W, Yan J, Li X. Parenteral
analgesics for pain relief in acute pancreatitis: a systematic review.
Pancreatology. 2013. 13:201-6.
12. Abdullah M, Firmansyah MA. Diagnostic approach and management of acute
abdominal pain. Acta Med Indones-Indones J Intern Med. 2012. 44 (4):34450.
13. Yamada T. Textbook of Gastroenterology. 5th Edition. California: Blackwell
Publishing Ltd. 2011.
14. Lankisch PG, Banks PA. Pancreatitis. New York: Springer Science &
Business Media. 2013. p. 75-153.
15. Waldman SD. Acute pancreatitis. In: Atlas of Common Pain Syndromes. 3rd
Edition. New York: Elsevier Health Sciences. 2011. p. 227-30.

16. Parikh AA, Seaberg DC. Pancreatitis. In: Wolfson AB, Hendey GW, Ling LJ,
Rosen CL. Harwood-Nuss Clinical Practice of Emergency Medicine. 5th
Edition. Philadelphia: Lippincott Williams & Wilkins. 2009. p. 581-6.
17. Sud R, Puri R. Acute pancreatitis: an overview. In: Garg PK. Acute
pancreatitis. India: Elsevier Health Sciences. 2013.
18. Perera MRS, Tattersall MZ, Wysocki AP. Analgesia in patients with acute
pancreatitis: a cry for help. International Journal of Gastroenterology
Research and Practice. 2014. 5:1-10.
19. Gardner TB. Acute Pancreatitis. Medscape. 2015. [Online] Available from:
http://emedicine.medscape.com/article/181364-medication [Accessed on 27th
May 2016].
20. Pezzilli R, Morselli L, Corinaldesi R. NSAIDs and acute pancreatitis: a
systematic review. Pharmaceuticals. 2010. 3:558-71.
21. Barreto SG, Saccone GTP. Pancreatic nociception revisiting the physiology
and pathophysiology. Pancreatology. 2012. 12:104-12.
22. Li Q, Peng J. Sensory nerves and pancreatitis. Gland Surgery. 2014. 3(4):28492.
23. Demir IE, Friess H, Ceyhan GO. Neural plasticity in pancreatitis and
pancreatic cancer. Natural Reviews Gastroenterology & Hepatology. 2015.
12:649-59.
24. Nelson KE, Habenicht AL. The patient with gastrointestinal problems. In:
Nelson KE, Glonek T. Somatic Dysfunction in Osteopathic Family Medicine.
Philadelphia: Lippincott Williams & Wilkins. 2007. p. 291-300.
25. Wuhrman E, Cooney MF. Acute pain: assessment and treatment. Medscape.
2011. [Online] Available from: http://medscape.com/viewarticle/735034
[Accessed on 9th June 2016].
26. DArcy YM. Meeting the challenges of acute pain management. Medscape.
2016. [Online] Available from: http://medscape.com/viewarticle/574105
[Accessed on 9th June 2016].
27. Petrov MS, Loveday B, Windsor JA. Management of acute pancreatitis and
complications. In: Jarnagin WR, et al. Blumgarts Surgery of the Liver,
Biliary Tract, and Pancreas. 5th Edition. Philadelphia: Elsevier. 2012. p. 84558.
28. Greenberg JA, Hsu J, Bawazeer M, Marshall J, Friedrich JO, Nathens A,
Coburn N, et al. Clinical practice guideline: management of acute
pancreatitis. Can J Surg. 2016. 59(2):128-40.